Shekhar Shashank, Liu Ruen, Travis Olivia K, Roman Richard J, Fan Fan
Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Institute of Clinical Medicine, University of Turku, Turku, Finland.
J Pharm Sci Exp Pharmacol. 2017;2017(1):21-27. Epub 2017 Oct 27.
Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function.
衰老和慢性高血压与血管平滑肌、内皮细胞及神经血管耦合功能障碍有关。这些功能障碍会导致肌源性反应和脑自动调节受损，从而削弱脑小动脉对高血压时升高压力下脑微循环的保护作用。慢性高血压会促使脑局部缺血，这是由于久坐的老年高血压患者在接受降压治疗时经常出现血压降低的情况。脑自动调节功能障碍会引发血脑屏障（BBB）渗漏，使循环中的炎性因子渗入大脑以激活神经胶质细胞。脑自动调节功能受损引发的炎症和缺血性损伤可导致神经元细胞死亡和突触功能障碍，进而促进认知缺陷。在这篇简短的综述中，我们总结了高血压和缺血性卒中所致认知缺陷中脑自动调节的发病机制和信号传导机制，并讨论了我们的新靶点，包括可能导致脑血管功能改变的20-羟基二十碳四烯酸（20-HETE）、γ-内收蛋白（Add3）和基质金属蛋白酶-9（MMP-9）。
